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Topical and Oral Photoprotection

Maria Ivonne Arellano Mendoza, MDHospital General de México Dr. Eduardo Liceaga

mariare1@yahoo.com

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Disclosure

I hereby certify that to the best of my knowledge, no aspect of my currentpersonal or professional circumstances places me in the position of havingprivate interest which is in conflict with any interest of the Academy or withmy obligations to the Academy.

I have participated in advisory boards with Sanfer, Pierre Fabre, Galderma,Bioderma

.

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Melasma Treatment

Aim:Reduce pigment intensity

Reduce pigmented area

Prevent recurrence

Effective photoprotectionAvoid sun exposureUse of sunscreenHat, clothes, sunglasses

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02

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Depigmentigng agents

Procedures

Avoid aggravant factorsLong term strategies for our patient

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Electromagnetic SpectrumConsiderations

IR-AVisible light

UVA

Penetrate all skin layersReach hypodermis

Oxidative damage

Infrared

RadiationVisible

Light38.9 - 45 %

%

UVR

5 - 6.8%0.5% UVB

6.3% UVA

Cho S et al. JJ Derm Sci.2008;50:123-133Svobodová A et al Int J Radiat Biol 2010;86:999-1030

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3

4

51

2Exposure to sunlight

1. Short term and long term consequences

2. Types of exposure defined and simulated

3. Extreme, INTENSE exposure, zenithal: erythema, DNA damage and mutation, immunosuppression, cancer

4. Non-extreme, non-zenithal exposure, daylight induced:1. Disturbed hydration and increased pigmentation

2. Dermis alterations: extracellular matrix composition

3. Altered keratinocytes, melanocytes & Langerhans cells

5. Oxidative stress

Marionnet C, Tricaud C, Bernerd F Exposure to Non-Extreme Solar UV Daylight: Spectral Characterization, Effects on Skin and Photoprotection. Int J Mol Sci Jan:16(1):68-90

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Effects of Visible Light on the SkinPortion of the electromagnetic radiation visible to the human eye (400-700 nm)

Exerts biologic effects on the skin:

Erythema, pigmentation, thermal damage

Free radical production

Indirect DNA damage generating ROS

Premature ageing

UVA1 and visible light induce pigmentation immediately

Darker and more sustained pigmentation

2 weeks duration, unchanged

Does not induce thymine dimers

formation

Increases tyrosinase activity and

multiple exposures induce pigmentation

in Caucasian skin (conditioning),

proinflammatory cytokines and matrix

metalloproteinase (MMP-I).

Mahmoud B. Hexsel C, Hamzavi I. Photochem. Photobio,2008,84:450-462

Parrado C, Mascaraque M, Giralbete Y, Gonzalez S Int.J.Mol.Sci. 2016,17,1026;doi:10.3390/ijms17071026

Mahmoud B. Ruvolo E, Hexsel C,et al. J Invest Dermatol 2010;130: 2092-2097

Cho S et al. JJ Derm Sci.2008;50:123-133Liebel F, Kaur S, Ruvolo E et al. J Invest Dermatol 2012;132: 1901-1907

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Infrared radiation

• Therapeutic doses 1-10 J/cm2*

• Generates free radicals in human skin

• Depletes levels of beta-carotene and lycopene in human skin

• Angiogenesis

• Increased number of mast cells

• Decreases keratinocytes turn over

• Decreases Langerhans cell density

*Parrado C, Mascaraque M, Giralbete Y, Gonzalez S Int.J.Mol.Sci. 2016,17,1026;doi:10.3390/ijms17071026

Importance

Kaye E, Levine J, Blank I et al. Arch Dermatol 1991;127: 351- 355

• Organic filters do not protect from visible light.

• Only optically opaque filters are able to absorb visible light

• The two available inorganic sunscreen agents are zinc oxide and

titanium dioxide

• Micronized forms of metal oxides, not only scatter and reflect light,

but also absorb UV

• In 1991, Dr. Kaye et al, described that opaque physical sunscreens

are useful blockers of visible light, and that transmittance of light can

be lowered by adding iron oxide.

Near Visible Light an UV Photoprotection in The Treatment of Melasma: A Double-Blind Randomized Trial

Castañedo-Cazeres JP, Hernández-Blanco D, Carlos-Ortega B et al Photodermatol Photoimmunol Photomed 2014;30:35-42.

S I M

Study fo efficacy of sunscreen with broad-spectrum UV protection that contains iron oxide as VL-absorbing pigment

VS

Regular UV- only broad-spectrum sunscreen

MASISubjective scaleColorimetryHistology (2)

Performed:Initial, week 2,4,6,8

68 melasma patientsRandomized in 2 groups

All recieved:One of two sunscreensHydroquinone 4% at night

Near Visible Light an UV Photoprotection in The Treatment of Melasma: A Double-Blind Randomized Trial

Castañedo-Cazeres JP, Hernández-Blanco D, Carlos-Ortega B et al Photodermatol Photoimmunol Photomed 2014;30:35-42.

MASI

(Reduction %)

UV-Vis : 78.8± 11

UV: 61-9 ± 16 Melanin fraction/mm² (reduction % w8)

UV-Vis: 32.8 ± 14

UV: 19.1 ± 11Mast cells

UV-Vis: 14.7±7

8±5

UV Only :16±12

12±10Global Physician Assessment

01

03

02

04 UV -Vis: 75%

UV: 47%

Prevention of Melasma Relapses with Sunscreen Combining Protection Against UV and Short Wavelenght of Visible Light:

A Prospective Randomized Comparative Trial

Passeron T. J Am Acad Dermatol 2015;72:189

Wavelenghts

Short wavelengths

(415 nm)

Induce prolonged pigmentation

Long wavelenghts (639 nm) do not affect pigmentation

Study

Performed real-life settings

Spring and summer

Looking at photoprotection against melasma relapse

Sunscreens: same UV filter

Formula A: Tinted/Iron Oxide

Formula B: Untinted/No Iron Oxide

Evaluation

MASI

Standarized pictures

2 physicians masked to sunscreen used

Results

Median increase of MASI score in 6 months was more important with the use of untinted only UV sunscreen

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ROS Formation and Effects

Denat L, Kaderakaro A.L., Marror L, J Invest Dermatol Lun;134(6):1512-1518

Ascenso A, Margarida Ribeiro, Cabral Marques et al Current Drug Delivery 2011;8:640-660

Ultraviolet radiationPollution

DrugsPesticidesTobacco

Exogenous

Factors ROS

Formation

Cell

Modifications

Oxidation reactionExcessive phagocytosis

Arachidonic Ac Metabolism activation

Endogenous

Factors

Collagen fibersGAGsElastin

Alterations of

Extracellular

Proteins

Melanocytes

Melanin

synthesis

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2

3

64

5

DNA lesionMembrane lipid

structure alterationCell proliferation

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3

AntioxidantsSubstances that offer protection to cell membranes and

prevent oxidative stress to the tissues of the body

by neutralizing toxic oxygen molecules and free radicals

AO ENZYMES

Catalyze reactions involved

in the conversion of free

radicals to oxygen

and water

Catalase

Glutathione peroxidase

Superoxide dismutase

CHAIN BREAKING AO

Prevent propagation of the

oxidative chain reactions

by terminating free

radicals or the reactive

products of molecules

that have been

damaged by free radicals

Vit E & C

Flavonoids

Uric acid

Bilirrubin/ albumin

Thiol group/albumin

PREVENTIVE AO

Metal binding proteins

that sequester free iron

or copper to prevent

production of the

OH Radical from other

free radicals

Ferritin

Transferrin

Lactoferrin

Ceruloplasmin

Antioxidants

Alvim Sant´anna Addor F. Ann Bras Dermatol 2017;92(3):356-62

Vitamin ENeutralization of singlet oxigen in cell

membrane, membrane stabilization,

preventing lipid peroxidation-oxidation of

unsaturated fatty acids such as arachidonic

acid

Vitamin CRemoval of free radicals and repair of

oxidized Vit E

Epigallocatechin gallate (Green tea) Flavonoid broad scavenging action, inhibits ROS production, protects endogenous antioxidative sistems

Polypodium leucotomosInhibition of UV induced ROS

generation, including superoxide anion

Carotenoids (Lutein, lycopene)Neutralization of singlet oxigen

Protection of fibroblasts from UVA

oxidative acction

Prevents depletion of catalase and SOD

ResveratrolInhibition of UV-Induced oxidative

and mutagenic action to DNA

Coenzyme Q10Production of free radicals and

regenerates Vit E,

UVA-induced metalloproteinase in

fibroblasts,

mitocondrial damage

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Photoprotection of Human SkinBeyond Ultraviolet Radiation

Grether-Beck S, Marini A, Jaenicke T. Photodermatol Photoimmunol Photomed 2014; 30: 167-174

Grether-Beck S, Marini A, Jaenicke et al. Photochem & Photobiol 2015; 91: 248- 250

Eberleing-Koning, Ring J J Cosm Dermatol 2005;4:4-9

Protection vs IRA is centered in the use of topical antioxidants

Vit C, Vit E, Ubiquinone

& grape-seed extract or

Ferulic acid, tocopherol & Vit C

For example:

Added to sunscreens and

daily care products

Only some of the combinations are

usefull for this purpose

Impacts in upregulation of

MMP-1 & MMP-1m RNA expression

TWO STEP STRATEGY

Antioxidative capacity & concentration

Stability in formulation

Skin penetration

Oral Antioxidants

* Grether-Beck, Marini A, Jaenicke et al Br J Dermatol 2017;176:1231-1240

Parrado C, Mascaraque M, Giralbete Y, Gonzalez S Int.J.Mol.Sci 2016;17:1026

Chou H et al Int. J. Mol. Sci. 2016; 17: 955

Yohihisa E, Rehman M, Exp Dermatol. 2014 Mar;23(3):17883

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Polypodium leucotomosHigh content in phenolic compounds

Reduces generation and release of ROS

by UVR & DNA damage

Reduces apoptosis & necrosis, and UVA

and MMP1 induced by visible light

2Astahanthine

Xantophil carotenoid

Cultured red algae

Lowers lipids and strong AO

Reduces UV induced inflammation

4

Oral antioxidants

Sufficient amounts in the right place

How long?

Dietary or supplements

3

Lycopene and luteine *

Capsules

Reduces UV-radiation induced mRNA

expression of HO-1, MMP-1 and ICAM-1

Protection vs short wave UVB/A and

longwave UVA1

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Ideal

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Reflect, absorb or refract light

Broad spectrum

Visible light & IRA

Avoid ROS generation

Easy uniform spread

Cosmetically accepted

Water

Sweat

Rub

Resistant

Non comedogenic

Hipoalergenic

Long lasting

Arellano I, Alcalá D, Barba J et al. Recomendaciones clínicas para la fotoprotección en México. Dermatología CMQ 2014;12(4):243-255

Lautenschlager S, Wulf HC, Pittelcow M. Photoprotection. Lancet 2007;370:528-37

Sunscreens

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Photoprotection Today Considerations

1Melasma patients need to understand

Photoprotection is the most important part of their treatment

2Stay away from the sun (11 am – 16 pm)

Seek the shadeUse hat, sunglass

3Recommend the best topical sunscreen

Tailored for each patient Many products available

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Topical antioxidants Two step strategy

Many of them have whitening action

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Oral photoprotectionRecognized as a coadyuvant strategy

Never as only measure

THANK YOU